Review of electrocardiographic abnormalities among people living with HIV in Sub-Saharan Africa: A systematic review

Introduction Electrocardiographic (ECG) abnormalities are increasingly being reported among people living with HIV (PLWH). However, the exact prevalence of ECG abnormalities among PLWH in Sub-Saharan Africa (SSA), a region with one of the highest burdens of HIV, is not known. Through a systematic review, we determined the prevalence and patterns of ECG abnormalities among PLWH in SSA. Methods We conducted a search in online databases including EMBASE, MEDLINE, CINAHL and Research for Life for studies published between 1st January 2000 and 31st December 2020. Studies reporting any form of ECG abnormalities published in English were screened and reviewed for eligibility. Retrieved studies were assessed for validity using the modified Newcastle-Ottawa Scale. Data was summarized qualitatively, and ECG abnormalities were further subcategorized into rate, conduction, and rhythm abnormalities as well as atrial and ventricular enlargements. Results We retrieved seventeen of the 219 studies assessed for eligibility published between 2001 and 2020, with a total of 2,572 eligible participants. The mean age of the participants ranged between 6.8 years and 58.6 years. Of the 17 studies, 8 (47%) were case-control, 6 (35.3%) cross-sectional and 3 (17.6%) were cohort in design. Thirteen studies were conducted in the adult population while four were conducted in the pediatric population. The prevalence of ECG abnormalities ranged from 10% to 81% and 6.7% to 26.5% in the adult and pediatric population respectively. Among studies done in the adult population, conduction abnormalities were the most reported (9 studies) with a prevalence ranging from 3.4% to 53.5%. In the pediatric population, rate abnormalities were the most reported (4 studies) with a prevalence ranging from 3.9% to 20.9%. The heterogeneity in results could be attributed to the absence of uniform criteria to define ECG abnormalities. Conclusion Our findings highlight a high prevalence of ECG abnormalities among PLWH in SSA. Consideration of ECG in the comprehensive evaluation of cardiac dysfunction among PLWH in SSA maybe warranted.

Thank you for the comments. These have been rectified.

Comment:
I find it very confusing to combine the pediatric data with the adult data, since you would expect VERY different prevalences of ECG abnormalities among these populations. I would consider breaking this into two separate tables with separate summary statements.

Response:
Thank you for the comment. A separate table for pediatric data has been created.

Discussion:
Comments: I think the discussion is missing several points and needs to be heavily re-written. Most of the Discussion consists of the authors citing random studies from other settings but not really synthesizing the data the presented in their results in a meaningful way. -You report a HUGE range of ECG abnormalities (6-81%) which is so large that the data is almost unhelpful. Please comment on why you think this range is so large with specific reference to study design, study population, etc. Since the studies evaluated different sets of ECG abnormalities, I don't think it's helpful to report this summary range because each study reported different kinds of ECG abnormalities.
Response: Thank you for comment. An explanation for the wide range has been added in line 219 to 243.

Comment:
-I think separating out the adult and pediatric studies would be more helpful for your discussion of the adults since the findings and clinical implications are so different.
Response: Thank you for the comment. Different tables have been created. Table 2 and Table 4 to cover the pediatric population.

Comments:
-I suggest you delete this sentence: "In a prospective cohort study involving 1,770 HIVinfected and 3350 HIV negative participants, ECG abnormalities were found in 35% of the HIV patients which was higher than 32.2% found in HIV negative individuals (43). This difference was statistically significant (p=0.04)." This adds nothing to your discussion, since you already reported results from a similar study in China (where this study was done). You also don't report comparative data between HIV-infected and HIV-uninfected so this is not relevant to your findings.
-When you discuss the SMART study, please specify which countries/regions this was in.
-Overall I think all of Paragraph 2 of the Discussion could be collapsed to a single sentence: "The prevalence of ECG abnormalities among ADULTS in our study was similar to what has been reported in high income settings" -Line 210, remove the word "likely" -Lines 212 to 219, please specify which country each of these cited studies were in.
-I suggest deleting lines 220-229, as these are redundant from the introduction.
-"ECG are easily accessible to most settings in SSA and could play a huge role in identify PLWH at a risk of developing severe CVDs if used routinely." I think both parts of this sentence are untrue. ECGs are certainly not widely available to people with HIV in a lot of parts of SSA. I don't think ECGs could identify those at risk of developing CVDs--more accurate to say that they could identify some forms of CVD such as arrhythmias and ischemia? -"Furthermore, it may play an important role in determining the prognosis of PLWH with suspected cardiovascular diseases." This statement is untrue. -Again, I think a separate paragraph about pediatric results would be helpful.
-Line 234, re-write as "which may have led to exclusion of other studies reporting ECG abnormalities among persons with HIV in SSA" -Line 235, re-write as "which likely resulted in significant heterogeneity in results" -Line 238: I don't think it's fair to say this review presents an "exact burden" as the ranges are so large and there is so much heterogeneity among studies.
Response: Thank you for the comments. These have been updated.

Comment:
-Please re-write all three Conclusion sentences as the written English is hard to follow.
Response: Thank you for the comment. The conclusion has been re-written.

Reviewer #2:
This is an important study that highlights a significant topic in which there is a large paucity of data in SSA. The manuscript will contribute to the growing body of cardiovascular disease literature in SSA and highlights the burden of disease and need for further action.
2. While the study appears to be sound, the language is unclear in some areas, making the manuscript difficult to follow at times. I would advise close review of the manuscript to ensure clarity and accuracy in the writing. I have included few lines below for some suggested changes for clarity.

Comments
Line 65 -would rephrase '78% of PLWH could have developed a CVD' to '78% of PLWH may develop CVD'.
Line 76 -would change 'such as arrhythmias, myocardial…' to 'arrhythmias and myocardial…' Line 79-81 -would rephrase 'With an increased population aging amongst PLWH, the prevalence of ECG abnormalities…' to 'With an increasingly aging population, the prevalence of ECG abnormalities among PLWH is likely to increase…'.
Line 137 -would change 'Rate' to lower case 'rate' Line 149 -would rephrase 'The studies were done in 7 African countries…' to 'The studies were conducted in 7 African countries'.
Line 230 -would change 'huge role in identify PLWH' to 'huge role in identifying PLWH' Response: Thank you for the comment. These have been updated.

Comment:
3. HIV-related characteristics of samples from the 17 studies are not described including duration of HIV, stage of HIV (i.e. well controlled/virologically suppressed vs advanced/untreated), current CD4, viral load (if available), if on ART, the type/class of ART, and the duration of ART. In addition, HIV-related characteristics were not taken into consideration in either the analysis or in the discussion. As HIV-related